Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study.

AIMS/INTRODUCTION: A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk. MATERIALS AND METHODS: This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods. RESULTS: Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97-1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98-1.04). Findings were also consistent across cancer types and sensitivity analyses. CONCLUSIONS: We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.

Quality of care measurement for patients with ovarian cancer in Japan.

AIM: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high-quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. METHODS: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2018. All patients receiving first-line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. RESULTS: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence. CONCLUSIONS: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.

BACKGROUND: In Japan, comprehensive cancer statistics data have been collected through national cancer registries, but these data are rarely summarized and reported in research articles. METHODS: Here, we compiled the national registry data on malignant tumors originating from gynecologic organs (ovary, corpus uteri, cervix uteri) in Japan. RESULTS: The number of new patients in 2019 was 13,380, 17,880, and 10,879, respectively, and the number of deaths in 2021 was 5081, 2741, and 2894, respectively. Compared with 40 years ago, the incidence of ovarian cancer has tripled, the incidence of uterine corpus cancer (mainly endometrial cancer) has increased eightfold, the mortality rate of uterine corpus cancer has tripled, and the incidence of cervical intraepithelial cancer has increased ninefold in data standardized by the world population. Compared with the United States, the incidence rate of ovarian cancer has overtaken and the mortality rate of uterine corpus cancer is the same, while both the incidence and mortality rates of cervical cancer are higher in Japan. CONCLUSION: The incidence of gynecologic cancer is increasing significantly in Japan.

Time to Treatment Initiation for Six Cancer Types: An Analysis of Data from a Nationwide Registry in Japan.

BACKGROUND: Delay in the time to treatment initiation (TTI) may adversely affect the survival of patients, but its current status in Japan is unknown. This study aims to describe the TTI for six cancer types: lung, breast, colorectal, stomach, head and neck (H&N), and cervical. Data for this study were derived from a nationwide registry in Japan. METHODS: This observational study employed the national database of hospital-based cancer registries (HBCRs) and health services utilization data. Using HBCR data, we identified all patients with cancer who started their cancer therapy at the same hospitals between January 1 and December 31, 2017. We calculated the TTI for each cancer type and treatment option, stratifying the results by age group and geographical region. RESULTS: The overall median TTI was 33 days, with shorter TTIs for colorectal and H&N cancers and chemotherapy. The TTI was the shortest for younger patients and the longest for the elderly, especially for lung cancer. When categorized by eight Japanese geographical regions, Tohoku and Kanto had the longest TTI. The result remained the same even after adjusting cancer type, treatment, age, and stage information. CONCLUSION: For colorectal and H&N cancers, in which a longer TTI is associated with a poorer prognosis, TTI was found to be particularly shorter. Although we could not discuss our results in light of the patient survival in this study, future research should explore the best balance between thorough evaluation before treatment and necessary time for that.

Pembrolizumab-related pancreatitis with elevation of pancreatic tumour markers.

Lung cancer immunotherapy is an effective treatment option; however, it can be hampered by adverse events, including pancreatitis, associated with excessive immune activation. Here, we report the case of a 70-year-old patient who presented with recurrent lung squamous carcinoma and was started with pembrolizumab treatment (200 mg every three weeks). The patient developed pembrolizumab-induced pancreatitis. After 14 months of pembrolizumab treatment, positron emission tomography-computed tomography showed a tumour-shaped, highly integrated lesion at the pancreatic head and significantly elevated tumour markers, including carbohydrate antigen 19-9 (149.3 U/mL), s-pancreas antigen-1 (44.7 U/mL), and duke pancreatic monoclonal antigen type 2 (412 U/mL). Pembrolizumab-induced immune-related pancreatitis was effectively treated with prednisolone 90 mg (1 mg/kg/day). Four months later, normal levels of the three specific tumour markers were detected, with improved pancreatic enzymes and radiographic findings. To our knowledge, this is the first reported case of immune-related pancreatitis with elevated pancreatic cancer-specific markers.

Cost-effectiveness of bronchial thermoplasty for severe asthmatic patients in Japan.

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

Can the Number of Radiofrequency Activations Predict Serious Adverse Events after Bronchial Thermoplasty? A Retrospective Case-Control Study.

INTRODUCTION: Bronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs. METHODS: We retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis. RESULTS: A total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs; p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; - 0.49 l/- 14.2%/- 0.36 l/- 11.7%/- 9.6% in sessions with SAEs; - 0.43 l/- 13.3%/- 0.34 l/- 12.1%/- 9.4% in sessions without SAEs; p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1 (R2 = 0.17, p = 0.0088) and %FEV1 (R2 = 0.11, p = 0.0357). CONCLUSIONS: Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

A successful treatment of rheumatoid arthritis-related interstitial pneumonia with nintedanib.

Rheumatoid arthritis-related interstitial pneumonia with a usual interstitial pneumonia (RA-UIP) has a poor prognosis and a new treatment strategy is required. The antifibrotic agent nintedanib reduces the annual rate of decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF) patients. Recently, the potential efficacy of antifibrotic agents against chronic progressive fibrotic diseases including RA-UIP has been attracting attention. A 74-year-old man diagnosed with IPF on high-resolution computed tomography (HRCT). His FVC was decreasing over time, and his exertional dyspnea and cough had progressed with progression of reticulation on imaging. He was treated with nintedanib, which resulted in decreased coughing together with a reduction in FVC decline, from -11.6%/year to -5.2%/year. A swollen joint appeared eight months after this intervention, and he was diagnosed with rheumatoid arthritis. In this patient, nintedanib was effective against RA-UIP. This is the first case in which nintedanib was shown to be effective for RA-UIP.